Bilirubinuria : Causes, Symptoms, Diagnosis & Treatment

Last Updated: 18/06/2022

Bilirubinuria is a pathological condition characterized by the presence of bilirubin in the urine. The causes are diseases of the liver and biliary tract (BI). A high concentration of bilirubin stains the urine dark brown. The test for bilirubinuria together with the test for urobilinogenuria (detection of bilirubin derivatives in the urine) is used for the differential diagnosis of jaundice - parenchymal, hemolytic, obstructive. Treatment of the underlying disease is necessary to correct bilirubinuria.

Causes of bilirubinuria

Physiological reasons

Physiological urobilinogenuria is often observed since small concentrations of bilirubin metabolites (up to 17 μmol / l) are always found in healthy urine. Bilirubin is also present in the urine of a healthy person (about 7-20 µmol/l), but this amount is not determined by standard methods. Therefore, the detection of bilirubin in the general analysis of urine always indicates some kind of pathology.


False bilirubinuria and urobilinogenuria are possible in patients taking drugs that color urine red (chlorpromazine, phenazopyridine, medazepam). This is due to the peculiarities of the chemical reactions of urinary test strips. This fact should always be taken into account when interpreting urinalysis results.

Liver disease

The main cause of bilirubinuria. When the liver parenchyma is damaged, bilirubin is released into the blood from the destroyed cells, both indirect and direct, i.e. associated with glucuronic acid (conjugated). When it enters the kidneys with the bloodstream, bilirubin enters the urine through the kidney filters, since the glomerular apparatus of the kidneys can pass conjugated bilirubin.

The level of bilirubinuria is insignificant at the initial stages of liver damage, then gradually increases in parallel with the severity of the process, reaching maximum figures in the peak stage, after which it begins to decrease under the influence of therapy. Bilirubinuria occurs in the following diseases:

  • Viral hepatitis.
  • Toxic hepatitis (alcoholic, drug).
  • Autoimmune hepatitis (AIH).
  • Cirrhosis of the liver.
  • Liver damage in severe infections: pneumonia, sepsis, infectious-toxic shock.
  • Liver damage in patients with metabolic diseases: hereditary or secondary hemochromatosis, Wilson-Konovalov disease, alpha-antitrypsin-1 deficiency.
  • Hepatocellular cancer.
  • Parasitic diseases: amoebic liver abscess, echinococcosis.

Dark urine is a sign of bilirubinuria


Diseases of the biliary tract

Very often, bilirubinuria is noted in diseases characterized by a violation of the outflow of bile (obstructive, subhepatic jaundice). Due to obstruction of the intrahepatic or extrahepatic biliary tract, hydrostatic pressure increases in their lumen. Conjugated bilirubin begins to diffuse into the blood capillaries, then it is filtered through the kidneys into the urine.

The degree of bilirubinuria is quite high from the very beginning of the disease, correlates with the severity of obstruction of the biliary tract, and disappears after its elimination - with surgical treatment almost immediately, with conservative therapy gradually. Diseases of the biliary tract, in which bilirubinuria is observed:

  • Calculous cholecystitis, cholelithiasis.
  • Purulent cholangitis.
  • Primary biliary cirrhosis (PBC).
  • Primary sclerosing cholangitis (PSC).
  • Cholangiocarcinoma.
  • Cancer of Vater's papilla.

Benign hyperbilirubinemia

A rather rare cause of bilirubinuria is hereditary disorders of bilirubin metabolism, namely Dubin-Johnson syndrome and Rotor syndrome. These disorders are characterized by a genetic defect in the system of transport of organic anions in the bile ducts, which disrupts the flow of conjugated bilirubin into bile.

Due to the accumulation of excess bilirubin in hepatocytes, part of it enters the blood, then into the urine. Bilirubinuria is insignificant and, since there is no specific treatment for these diseases today, it is observed throughout the patient's life.

Causes of urobilinogenuria

Urobilinogen are derivative of bilirubin. Their detection in urine is considered an important diagnostic tool. The presence of urobilinogen in the urine can occur with increased destruction of erythrocytes (hemolytic conditions), lesions of the liver parenchyma, and increased reabsorption in the distal colon.

With viral hepatitis, urobilinogenuria reaches its maximum values ​​at the beginning of the disease, then gradually decreases and is practically not detected during the peak of the disease and increases again during recovery. Diseases in which urobilinogenuria occurs:

  • Diseases accompanied by hemolysis: hemolytic anemia, hemoglobinopathies, and conditions after blood transfusions.
  • Liver diseases: viral, toxic hepatitis, liver cancer.
  • Intestinal diseases: enterocolitis, prolonged constipation, intestinal obstruction.

Causes of urobilinogenuria with bilirubinuria

The simultaneous presence of urobilinogen and bilirubin in the urine is characteristic of parenchymal jaundice, i.e. liver diseases. The detection of these 2 laboratory analytes is an important step in the differential diagnosis of jaundice. The combination of bilirubinuria and urobilinogenuria is observed at the onset of acute liver disease (for example, in the pre-icteric stage of acute viral hepatitis) or in the presence of a chronic inflammatory process in the liver tissue (autoimmune hepatitis, chronic viral hepatitis).


If bilirubinuria is detected, you should consult a general practitioner to find out the causes of its occurrence. Bilirubinuria is a fairly early sign of damage to the hepatobiliary system, its occurrence often precedes the development of a vivid clinical picture of the disease. At the reception, an examination is carried out, during which attention is paid to the color of the skin and mucous membranes, liver enlargement, and symptoms of gallbladder damage (Kera's symptom, Ortner's).

Clarify the change in the color of urine and feces. When collecting anamnestic data, find out what medications the patient is taking. The level of bilirubin and urobilinogen is examined in the clinical analysis of urine using test strips. False-negative results are possible with long-term exposure of the urine sample to the light (oxidation of bilirubin and urobilinogen occurs), and a high concentration of ascorbic acid in the urine.

Microscopic examination of urine sediment in some cases reveals bilirubin crystals. To clarify the etiological factor of bilirubinuria and conduct a differential diagnosis, the following examination is prescribed:

  • Blood tests. In the case of liver diseases in the biochemical analysis of blood, an increase in the concentration of bilirubin, and liver enzymes (ALT, AST) is noted, and in diseases of the gastrointestinal tract - and increase in cholestasis markers (alkaline phosphatase, gamma-glutamyl transpeptidase), in hemolytic conditions - lactate dehydrogenase, indirect bilirubin. In people with metabolic disorders, indicators of transferrin, ceruloplasmin, and metal ions (copper, iron) in the blood are determined.
  • Immunological research. If viral hepatitis is suspected, ELISA and PCR are prescribed to detect specific antibodies (HBsAg, HCV), DNA, and RNA of viruses. In autoimmune disorders, autoantibodies are examined - antimitochondrial, anticytoplasmic, antibodies to smooth muscle cells.
  • Hemolysis tests. To confirm hemolysis, the determination of the osmotic resistance of erythrocytes, the Coombs test, electrophoresis of hemoglobin proteins, flow cytometry, etc. are carried out.
  • ultrasound. Ultrasound of the abdominal organs can reveal an increase in the liver, a decrease in its echogenicity, diffuse changes, thickening of the walls of the gallbladder, and the presence of calculi.
  • Genetic research. In case of suspicion of benign hyperbilirubinemia as the cause of bilirubinuria, genetic tests are prescribed to detect mutations by cytogenetics, and polymerase chain reaction.

Diagnosis of bilirubinuria



Conservative therapy

Methods for self-correction of bilirubinuria, as well as urobilinogenuria, do not exist. It is necessary to treat the underlying disease. In the case of liver diseases, restrictive measures are taken first of all - the appointment of a dietary table No. 5 according to Pevzner, the refusal to drink alcohol, and the abolition of the drug (in the case of drug-induced hepatitis). Also, depending on the cause, the following medicines are used:

  • Antivirals. Related interferon, nucleoside analogs (entecavir, ribavirin), and reverse transcriptase inhibitors (lamivudine) are used to treat viral hepatitis.
  • Choleretic drugs. In diseases accompanied by cholestasis, drugs containing ursodeoxycholic acid are effective.
  • Hepatoprotectors. To protect liver cells from excessive damage, ademetionine, and glycyrrhizic acid are used.
  • Glucocorticoids. Adrenal hormone preparations (prednisolone, methylprednisolone) are used to suppress autoimmune inflammation in AIH, PSC, and PBC.
  • Drugs to combat hemolysis. To prevent hemolysis, immunosuppressants (hydroxyurea), and intravenous immunoglobulin are prescribed. To stop crises, they resort to narcotic and non-narcotic analgesics.
  • Antiparasitic agents. For amebiasis, metronidazole, ornidazole are used, for echinococcosis - mebendazole.
  • Chemotherapy. Patients with hepatocellular carcinoma or cholangiocarcinoma are prescribed multikinase inhibitors (sorafenib, lenvatinib).


In patients with calculous cholecystitis and cholelithiasis, surgical removal of the gallbladder (cholecystectomy) is indicated. Currently, endoscopic operations with minimal trauma are predominantly performed. With echinococcosis, a cyst is removed. The most effective treatment for many diseases associated with hemolysis is splenectomy (removal of the spleen).

After this operation, to prevent infectious complications, vaccination against pneumococcus, meningococcus, and Haemophilus influenza is mandatory. For some diseases, such as liver cancer, cholangiocarcinoma, and sclerosing cholangitis, the only way to prolong the patient's life is through liver transplantation.


Bilirubinuria, like urobilinogenuria, cannot be a predictor of prognosis. It all depends on the underlying pathology, against which these laboratory abnormalities arose. The most favorable prognosis is benign hyperbilirubinemia and viral hepatitis A. The most unfavorable outcomes are observed with oncological diseases, cirrhosis of the liver, and fulminant course of acute hepatitis. Therefore, in case of detection of bilirubinuria, it is necessary to contact a specialist.

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